tbuckley/cabot-search huggingface dataset:
Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer: A multi-center, open-label, single-arm, phase II study.
Authors: Peijian Peng, Xiaolu Xu, Jincai Zhong, Hong Lin, Hong Wang, Jin-Hui Ye, Caiwen Du, Zhi-Hui Wang, Gengsheng Yu, Guorong Zou, Jie Ouyang, Yong-Xia Wang, Lu-Zhen Li, Fei Xu, Shi-En Cui
Journal: Journal of Clinical Oncology (2023)

e13102 Background: Eribulin is a non-taxane microtubule inhibitor approved in China for the treatment of patients with advanced breast cancer who progress after ≥2 lines of chemotherapy. Eribulin was shown to improve overall survival (OS) in various subgroups of patients with metastatic breast cancer (MBC) who were pretreated with an anthracycline and taxane. Furthermore, combination chemotherapy with eribulin plus gemcitabine led to a similar progression free-survival (PFS) benefit, with less neurotoxicity, as paclitaxel plus gemcitabine in patients with MBC who had not received prior cytotoxic chemotherapy for metastatic disease. However, the effect of eribulin plus gemcitabine on PFS in second-line or beyond remain unclear. Methods: This phase II, open-label, single-arm study was conducted at 13 institutions in China (NCT05263882). Patients with histologically confirmed HER2-negative MBC who had received at ≥1 prior taxane-containing chemotherapeutic regimen for advanced disease and had received anthracycline-containing regimens in the adjuvant setting, were enrolled between Nov 2021 and Oct 2022. Eligible patients received eribulin 1.4 mg/m 2 and gemcitabine 1.0 g/m 2 intravenously on days 1 and 8 of a 21-day cycle. Efficacy outcomes included PFS, objective response rate (ORR), and disease control rate (DCR), evaluated using RECIST v1.1. Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: In total, 54 patients were included; 39 (72.2 %) were HR+/HER2- and 15 (27.8 %) were triple negative, the median age was 49.5 years (range: 31-70) and sites of metastasis were the liver (57.4%), lung (37.0%), bone (59.3%), brain (11.1%) and lymph nodes (53.7%). The median number of previous chemotherapy lines was 3 (range: 2-7): eribulin plus gemcitabine was used in second-line for 15 (27.8%) patients, third-line for 20 (37.0%) patients, fourth-line for 7 (13.0%) patients and ≥fifth-line in 12 (22.2%) patients. The median PFS was 7.7 months. The ORR was 40.7% and the DCR was 66.7%. Best overall responses and PFS rates at 3 and 6 months are shown. The most common grade 3-4 AEs were hematological: Leukopenia (35.2%), anemia (18.6%) and thrombocytopenia (9.4%). No treatment-related death was reported. Conclusions: Eribulin plus gemcitabine is effective in heavily pretreated patients with HER2-negative MBC with a predictable, manageable safety profile. Clinical trial information: NCT05263882 . [Table: see text]
Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
Authors: Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal, Mehdi Touat, Katherine B. Peters, Jennifer Clarke, Joe Mendez, Shlomit Yust-Katz, Liam Welsh, Warren P. Mason, François Ducray, Yoshie Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger, Yoshiki Arakawa, Juan M. Sepulveda, Wolfgang Wick, Riccardo Soffietti, James R. Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Steven Schoenfeld, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, Timothy F. Cloughesy
Journal: New England Journal of Medicine (2023)

Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumors that cause considerable disability and premature death. Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas.
Lost in translation? Information exchange during breast cancer care and implications for technology design.
Authors: Megan Salwei, Carrie Reale
Journal: Journal of Clinical Oncology (2023)

1558 Background: Almost 4 million women in the US have had breast cancer, with 300,000 women diagnosed each year. Treatment decision-making following breast cancer diagnosis can be challenging as there are often several clinically appropriate treatment options, each with differing impacts on patient short- and long-term quality of life. Further, patients must manage this information during a time of high emotional burden, which can hinder decision-making. Not surprisingly, studies have found that less than 50% of patients believe their treatment plan aligns with their preferences. Numerous decision aids have been developed to support patient decision-making. However, sustained use of decision aids is limited due to poor integration in clinical workflow. We need to better understand the complex workflows and needs of decision aid users - patients and breast cancer clinicians. In this study, we investigate the information exchange between patients and clinicians when making breast cancer treatment decisions and identify design requirements for patient-centered decision support tools. Methods: This study is part of a larger research project to design a COMputerized PAtient-centered Collaborative Technology (COMPACT) to support personalized breast cancer decision-making. We observed clinicians at one academic medical center’s breast center from February-August 2022. Participating clinicians were followed throughout their clinical shift. Using a tablet computer and smart pencil, we recorded all aspects of clinician workflow. Written notes were transcribed and uploaded into Dedoose. Two human factors researchers inductively coded each observation in a consensus-based process. Results: We observed 79 hours of clinical care and 119 patient encounters across 20 observations of various clinical roles. Overall, we found that patients with breast cancer must manage an enormous amount of highly complex information that includes technical medical terms, mathematical concepts (e.g., risk), and uncertainty. We identified over 20 distinct decisions that patients face during their cancer journey, which were interdependent and evolved over time. We identified numerous patient-specific factors that influenced treatment decision-making, such as the patient’s work and family circumstances. For instance, one patient was organizing a conference and needed to plan her surgery around this event. Patients were frequently asked to remember and relay information across members of the care team, indicating inadequate system support of information transfer within the large cancer team. Based on these findings, we identified design requirements for interventions to support care coordination and patient-centered decision-making. Conclusions: These findings can inform the design of interventions to support breast cancer decision-making and improve patient-centered cancer care.
Neoadjuvant HER2-targeted therapy ± immunotherapy with pembrolizumab (neoHIP): An open label randomized phase II trial.
Authors: Heather L. McArthur, Jorge Leal, Stephen Lawrence Shiao, Meredith Carter, Reva K Basho, Michelle Phillips, David Chan, Hugo Hool, Dorothy J. Park, Mary El-Masry, Philomena McAndrew, Swati Sikaria, Laura Spring, Aditya Bardia, Mourad Tighiouart, Farnaz Dadmanesh, Armando E. Giuliano, Katherine Sanchez, David B. Page
Journal: Journal of Clinical Oncology (2023)

TPS634 Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxics; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are explored. Methods: Patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer are being randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts received T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts received THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts received TH-K. After enrollment of 22 pts to arm C, a prespecified interim efficacy analysis was conducted, and enrollment to this arm was subsequently terminated. Enrollment to the other arms continues with 32/58 pts enrolled to arm A and 33/58 pts enrolled to arm B as of 2/14/2023. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion per local clinical standard. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity. Clinical trial information: NCT03747120 .
National trends in neoadjuvant chemotherapy utilization for cT1-2 N0 triple negative breast cancer: Did the CREATE-X trial impact treatment patterns?
Authors: Christine Rogers, Jan Irene Lloren, Morgan K. Johnson, Adrienne Cobb, Lubna Naaz Chaudhary, Chiang-Ching Huang, Mediget Teshome, Puneet Singh, Amanda L. Kong, Chandler Scott Cortina
Journal: Journal of Clinical Oncology (2023)

e12599 Background: Neoadjuvant chemotherapy (NAC) for operable breast cancer allows for in-vivo assessment of chemotherapy response with survival and therapeutic implications. In 2017, the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial demonstrated significant improvement in survival with the addition of adjuvant capecitabine in patients with triple negative breast cancer (TNBC) and residual disease after NAC. These results provided the rationale for NAC even in early stage TNBC. The aim of this study was to assess U.S. national rates of NAC utilization in early-stage node-negative TNBC patients before and after the release of CREATE-X and to assess factors associated with receiving NAC vs adjuvant chemotherapy (AC). Methods: The National Cancer Database was queried for women with cT1-2N0M0 TNBC from 2014–19. NAC utilization was collected and categorized as 2014-15 (pre-CREATE-X), 2016-17 (transition yrs), and 2018-19 (post-CREATE-X). Those who did not receive chemotherapy were excluded. NAC use over time was analyzed via multivariable logistic regression (MLR). Clinical and demographic factors associated with NAC vs AC utilization were assessed using ANOVA, Chi-squared, and Fisher Exact tests. A MLR model was used to determine predictors of receipt of NAC vs AC. Results: 55,633 women were treated from 2014-19: 26.9% with NAC, 52.4% with AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71yrs, respectively, p &lt; 0.01). Most had cT1c (32.7%, n = 18,190) or cT2 (41.95%, n = 23,331) tumors and 99% had invasive ductal pathology. NAC utilization significantly increased over time, 19.5% (n = 3,465 of 17,777) in 2014-15, 27.1% (n = 5,140 of 18,985) in 2016-17, and 33.6% (n = 6,337 of 18,871) in 2018-19 (p &lt; 0.01). On MLR analysis, increased use of NAC was associated with younger age ( &lt; 50yrs), non-Hispanic white patients, having no comorbidities, having a cT2 tumor, grade 2 disease, and care at an academic or integrated network cancer program (p &lt; 0.05 for all). Patients with Medicare and Medicaid insurance were less likely to receive NAC (p &lt; 0.01). Patients who traveled &gt; 60 miles to their treating facility were more likely to receive NAC (p &lt; 0.01). Conclusions: From 2014–19, NAC utilization increased for patients with cT1-2N0M0 TNBC coinciding with the release of the CREATE-X results. Findings demonstrate the significance of the multidisciplinary oncology team in developing individualized treatment plans based on emerging clinical trial evidence. Racial, socioeconomic, and access disparities were observed in NAC utilization and warrants further investigation and interventions to ensure equitable care. [Table: see text]
Preoperative Treatment of Locally Advanced Rectal Cancer
Authors: Deborah Schrag, Qian Shi, Martin R. Weiser, Marc J. Gollub, Leonard B. Saltz, Benjamin L. Musher, Joel Goldberg, Tareq Al Baghdadi, Karyn A. Goodman, Robert R. McWilliams, Jeffrey M. Farma, Thomas J. George, Hagen F. Kennecke, Ardaman Shergill, Michael Montemurro, Garth D. Nelson, Brian Colgrove, Vallerie Gordon, Alan P. Venook, Eileen M. O’Reilly, Jeffrey A. Meyerhardt, Amylou C. Dueck, Ethan Basch, George J. Chang, Harvey J. Mamon
Journal: New England Journal of Medicine (2023)

Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. Download a PDF of the Research Summary. We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P=0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.) QUICK TAKE VIDEO SUMMARYPreoperative FOLFOX for Rectal Cancer 02:13
Use of the genetic signature of 70-genes MammaPrint in comparision with the immunohistochemical profile to de-escalate systemic treatment in the elderly population: Real-world study (AGEMA-BR).
Authors: Fabio Mansani, Ruffo Freitas-Junior
Journal: Journal of Clinical Oncology (2023)

e12561 Background: the elderly population, generally, presents a lower performance and greater susceptibility to complications and adverse effects of therapies, inferring that the de-escalation of cytotoxic therapies is desirable. Genetic signatures, including MammaPrint/ BluePrint, are the most appropriate tools to select among estrogen receptor (ER) patients with high clinical risk, who could, with oncological safety, not receiving adjuvant chemotherapy. Objective – to evaluate the performance of MammaPrint™ (MP) / BluePrint (BP) and the immunohistochemical profile (IHC) in the de-escalation of systemic therapy in the elderly population with breast cancer and Luminal profile. Methods: from the patients in the AGEMA-BRA study, which analyzes the performance of the 70-gene MammaPrint™ platform in the Brazilian population, those aged 70 years or older, with high clinical risk, who had data on the immunohistochemical profile available (37 patients). A comparative analysis was performed between the genomic profile (Luminal A/B on BluePrint; high and low risk on MammaPrint™ and the immunohistochemical profile (considered Luminal A with ER &gt;10%, RP&gt;10%, HER2 negative, Ki67 ≤20% Luminal B with ER&gt;10%, HER2 negative, Ki67&gt;20%) and clinical endpoints including disease-free survival (DFS) and overall survival (OS). Data analysis used accuracy and the Kappa coefficient (considering concordance &gt;0, 6). Results: mean age at diagnosis 73.1 years (70–80 years) and mean follow-up (FU) of 42 months. Of the 15 patients with high risk / luminal B by MP / BP, 5 were classified as luminal A by the IHC profile with a disagreement of 33.33%; of the 22 low-risk / luminal A patients by MP/BP, 6 were classified as luminal B by the IHC, a disagreement of 27.27%. Statistical analysis showed an accuracy between the IHC profile and the MP of 70.27%. The use of the IHC profile, when compared with the MP/BP, showed a sensitivity of 66.7% and a specificity of 72.7%. Of the 14 patients at high risk due to MP, 2 did not undergo chemotherapy treatment. All patients (at high and low risk) received adjuvant endocrine therapy with an aromatase inhibitor. After 42 months of medium FU, all patients were alive and disease-free, inferring DFS and OS of 100%. Conclusions: the analysis of data and outcomes in the elderly population of the AGEMA-BRA study with high clinical risk, demonstrated limited accuracy and low agreement in the stratification into high and low risk between the profile by IHC and the MP/BP. The use of the genomic platform may have been relevant in risk stratification and outcomes in this population. Studies with a larger sample and longer FU are needed to confirm the usefulness of genetic signatures in the de-escalation of systemic treatment in the elderly population with high clinical risk.
Utility of Ki67 in guiding adjuvant abemaciclib therapy for patients with hormone receptor (HR)-positive, early breast cancer (EBC).
Authors: Rima Patel, Nadeem Bilani, Amy Tiersten, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2023)

559 Background: The monarchE trial found that the addition of adjuvant abemaciclib to endocrine therapy in pts with lymph node (LN)+, HR+ EBC improved invasive disease-free survival in two pt cohorts: (1) ≥ 4 +LNs or 1-3 +LNs and Grade 3 disease or tumor ≥ 5 centimeters and (2) 1-3 +LNs and Ki67 ≥ 20%. The FDA approved adjuvant abemaciclib only in pts with HR+, HER2-negative, LN+ EBC with Ki67 ≥ 20%. The role of Ki67 as a predictive biomarker in this setting is unclear. ASCO guidelines recommend offering abemaciclib to pts who meet eligibility for either cohort and not restricting inclusion by Ki67. The objectives of this study were to (1) determine the association between Ki67 and the 21-gene recurrence score (RS), an established prognostic and predictive biomarker, using Ki67 cutoff ≥ 20% and (2) compare eligibility for adjuvant abemaciclib by FDA versus ASCO criteria. Methods: Women with HR+, HER2-negative EBC with 1-3 +LNs, diagnosed between 2018 and 2019, and who had available information on Ki67 and RS in the National Cancer Database were identified. Pts were categorized into Ki67 low ( &lt; 20%) or high ( ≥ 20%) based on cutoff used in the monarchE and stratified by RS of low-intermediate (0-25) or high (26-100). Stratified agreement between Ki67 and RS were assessed using the proportion of agreement and Kappa statistic. McNemar’s test was used to compare proportion of pts eligible for abemaciclib by FDA versus ASCO criteria. Results: 5,137 eligible women were included. 61.1% (n = 3,140) had Ki67 &lt; 20% and 38.9% (n = 1,997) Ki67 ≥ 20%. There was fair agreement (Kappa 0.21-0.40) between Ki67 and RS, which was statistically significant (Kappa = 0.25, p &lt; 0.001). Overall, using the FDA criteria for abemaciclib, 38.9% (n = 1,997) of patients would be eligible while based on ASCO criteria, 43.5% (n = 2,235) could be offered adjuvant abemaciclib (p &lt; 0.001). Among the 2,235 patients eligible for abemaciclib based on ASCO criteria, 57.0% (n = 1,273) were eligible due to Ki67 ≥ 20% alone, 10.6% (n = 238) due to Grade 3 alone, while 32.3% (n = 724) satisfied both Ki67 ≥ 20% and Grade 3 criteria. There were 3,431 patients who were post-menopausal with RS 0-25 and would be spared chemotherapy, yet 35.3% (n = 1,212) would be eligible for adjuvant abemaciclib based on FDA or ASCO criteria. Conclusions: There was only fair agreement between Ki67 and RS in patients with 1-3 +LNs based on Ki67 cutoff of 20%. Among patients with LN+ EBC, more patients would be offered abemaciclib using ASCO criteria compared to FDA criteria. Most were eligible for abemaciclib based on Ki67 alone, suggesting that Ki67 may provide additional information beyond tumor grade. In postmenopausal women with 1-3 +LNs, about 30% may be spared adjuvant chemotherapy based on the RS but still be sufficiently high risk to be considered for adjuvant abemaciclib.